依达拉奉动脉内给药对脑缺血再灌注损伤神经保护作用的研究

Intraarterial administration of edaravone can attenuate cerebral ischemia-reperfusion injury in rats

目的探讨依达拉奉动脉内给药对脑缺血的神经保护作用。方法将84只SD大鼠随机分为假手术组、模型组、动脉给药组及静脉给药组,采用线栓法制备大鼠大脑中动脉缺血再灌注模型。于再灌注4h后检测梗死半球脑组织超氧化物歧化酶(SOD)活力及丙二醛(MDA)含量;再灌注24 h后采用5点评分量表评价各组大鼠神经功能缺损情况,TTC染色后评估梗死体积,TUNEL法计数梗死区凋亡神经细胞,免疫组化法评估基质金属蛋白酶-9(MMP-9)表达水平。结果再灌注24 h后,与模型组比较,动脉给药组与静脉给药组的神经行为评分显著升高,梗死体积显著缩小,平均凋亡指数显著降低(均P<0.05)。与静脉给药组相比,动脉给药组梗死体积和平均凋亡指数显著降低(均P<0.05),神经行为评分差异无统计学意义(均P>0.05)。再灌注4 h后,与模型组比较,动脉给药组与静脉给药组MDA含量均显著降低,SOD活力显著升高(均P<0.05),而动静脉组间相比无统计学差异(均P>0.05)。与静脉给药组比较,动脉给药组MMP-9水平显著减少(P<0.05)。结论缺血再灌注后经动脉单次给予依达拉奉可以显著抑制MMP-9表达,减少神经细胞凋亡,较静脉单次给药效果更佳。

Objective To investigate the effect of intraarterial administration of edaravone on cerebral ischemiareperfusion neuronal apoptosis in rats. Methods Eighty-four SD rats were randomly divided into sham operation group,model group,intraarterial administration group and Intravenous administration group. The model of middle cerebral artery occlusion（MCAO） was made by intraluminal catheterization. The rats were injected with edaravone and reperfused for 4 hours,superoxide dismutase（SOD） activity and malondialdehyde（MDA） concentration in the infarcted regions were measured. After reperfusion for 24 h,the neurological deficit score,the infarct volume,matrix metalloproteinase-9（MMP-9） expression and apoptotic index were evaluated by Five-point score,TTC staining,Immunohistochemistry and TUNEL methods, respectively. Results After 24 h of ischemia-reperfusion,the neurological deficit of intravenous and intraarterial administration groups were both higher than that in model group（all P 〈 0. 05）,what’s more,the infarct volume and the apoptotic index of the two groups obviously decreased（all P 〈0. 05）. Although there was no significant difference in neurological deficit between intravenous and intraarterial administration groups（all P 〉 0. 05）,the infarct volume and the apoptotic index of intraarterial administration group obviously decreased as campared to intravenous administration group（all P 〈 0. 05）. Compared with modal group,the concentration of MDA and the activity of SOD of the intravenous and intraarterial administration groups after reperfusion for 4 h were both decreased and up-regulated,separately（all P 〈 0. 05）. Surprisingly,there was no significant difference between the two groups in MDA and SOD（all P 〉 0. 05）. In contract,the expression of MMP-9 in arterial administration group after 24 h of ischemia-reperfusion obviously decreased as compared to intravenous administration group（P 〈 0. 05）. Conclusion In the rat MCAO model,intraarterial administration of edaravone with signal dose can effectively inhibit MMP-9 expression incerase and prevent neuronal apoptosis after reperfusion,which provide a supplemental therapy for acute ischemic stroke after recanalization of blood vessels.